fondaparinux and Syndrome

Accomplishing a successful percutaneous coronary intervention in a patient with a suspected or diagnosed heparin-induced thrombocytopenia (HIT) requires the selection of an appropriate alternative anticoagulant and a thorough assessment of bleeding and thrombotic risks. In this review, we suggest an evidence-based management algorithm that takes into account the clinical phase of HIT (acute, recent, and remote HIT) and the associated risk when patients present with acute coronary syndrome. The algorithm also integrates preventive measures directed at decreasing the bleeding risk associated with the antithrombotic and invasive therapies used for HIT and percutaneous coronary intervention.

Topics: Algorithms; Angioplasty, Balloon, Coronary; Anticoagulants; Arginine; Chondroitin Sulfates; Comorbidity; Dermatan Sulfate; Drug Therapy, Combination; Fibrinolytic Agents; Fondaparinux; Heparin; Heparinoids; Heparitin Sulfate; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Pipecolic Acids; Polysaccharides; Recombinant Proteins; Sulfonamides; Syndrome; Thrombocytopenia; Vitamin K

The anticoagulant properties of heparin were discovered in 1916, and by the 1930s researchers were evaluating its therapeutic use in clinical trials. Treatment of unstable angina with unfractionated heparin (UFH), in addition to aspirin, was introduced into clinical practice in the early 1980s. UFH was combined with aspirin to suppress thrombin propagation and fibrin formation in patients presenting with acute coronary syndromes (ACS) or patients undergoing percutaneous coronary intervention (PCI). However, UFH stimulates platelets, leading to both activation and aggregation, which may further promote clot formation. Clinical trials have demonstrated that newer agents, such as the low-molecular-weight heparins (LMWHs), are superior to UFH for medical management of unstable angina or non-ST-segment elevation myocardial infarction. Increasingly, the LMWHs have been used as the anticoagulant of choice for patients presenting with ACS. For patients undergoing PCI, LMWH provides no sub-stantial benefit over UFH for anticoagulation; however, direct thrombin inhibitors (DTIs) have demonstrated safety and efficacy in this setting. UFH is likely to be replaced by more effective and safer antithrombin agents, such as DTIs. DTIs have antiplatelet effects, anticoagulant action, and most do not bind to plasma proteins, thereby providing a more consistent dose-response effect than UFH. The FDA has approved 4 parenteral DTIs for various indications: lepirudin, argatroban, bivalirudin, and desirudin. The antiplatelet, anticoagulant, and pharmacokinetic properties of bivalirudin support its use as the anticoagulant of choice for both lower- and higher-risk patients, including those undergoing PCI.

Topics: Acute Disease; Angina Pectoris; Angina, Unstable; Angioplasty, Balloon, Coronary; Anticoagulants; Arginine; Fondaparinux; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Hirudins; Humans; Models, Molecular; Molecular Structure; Myocardial Ischemia; Peptide Fragments; Pipecolic Acids; Platelet Activation; Polysaccharides; Recombinant Proteins; Sulfonamides; Syndrome; Thrombin; Thrombosis

The OASIS-6 trial demonstrated the benefit of fondaparinux in patients with ST-segment elevation myocardial infarction (STEMI) not undergoing primary percutaneous coronary intervention. Elderly compared to younger patients are at higher risk of bleeding and could have a different balance of benefits and risks when treated with antithrombotic therapy.. We explored the efficacy and safety of fondaparinux compared to control according to age tertiles in 12,092 patients with STEMI in the OASIS-6 trial. Death or myocardial infarction rates were reduced by fondaparinux in tertile I (age<56 years, 4.5% vs 4.8%, hazard ratio [HR] 0.94, 95% CI 0.71-1.25), in tertile II (age 56-68 years, 7.9% vs 9.7%, HR 0.80, 0.65-0.98), and in tertile III (age≥69 years, 17.2% vs 19.8%, HR 0.87, 95% CI 0.75-1.01, P for heterogeneity=0.87). Severe hemorrhage rates were reduced in tertile I (0.5% vs 0.6%, HR 0.94, 95% CI 0.41-2.12), in tertile II (0.9% vs 1.5%, HR 0.63, 95% CI 0.35-1.11), and in tertile III (2.1% vs 2.4%, HR 0.86, 95% CI 0.56-1.33, P for heterogeneity=0.86). Death, myocardial infarction, or severe hemorrhage rates were reduced in tertile I (4.8% vs 5.0%, HR 0.95, 95% CI 0.72-1.25), in tertile II (8.1% vs 10.1%, HR 0.79, 95% CI 0.65-0.97), and in tertile III (17.6% vs 20.4%, HR 0.86, 95% CI 0.74-1.00, P for heterogeneity=0.77).. The balance of benefits and risks of fondaparinux is consistent across age tertiles, supporting its use across the age spectrum of patients with STEMI who do not undergo primary percutaneous coronary intervention.

Topics: Aged; Anticoagulants; Coronary Angiography; Dose-Response Relationship, Drug; Electrocardiography; Factor X; Female; Follow-Up Studies; Fondaparinux; Humans; Male; Middle Aged; Myocardial Infarction; Polysaccharides; Syndrome; Treatment Outcome

A recent randomized, controlled trial, the Fifth Organization to Assess Strategies in Acute Ischemic Syndromes (OASIS 5) trial, reported that major bleeding was 2-fold less frequent with fondaparinux than with enoxaparin in acute coronary syndromes (ACS). Renal dysfunction increases the risk for major bleeding.. To compare the efficacy and safety of fondaparinux and enoxaparin over the spectrum of renal dysfunction observed in the OASIS 5 trial.. Subgroup analysis of a randomized, controlled trial.. Patients presenting to the hospital with non-ST-segment elevation ACS.. 19,979 of the 20,078 patients in the OASIS 5 trial in whom creatinine was measured at baseline.. Death, myocardial infarction, refractory ischemia, and major bleeding were evaluated separately and as a composite end point at 9, 30, and 180 days. Glomerular filtration rate (GFR) was calculated by using the Modification of Diet in Renal Disease formula.. The absolute differences in favor of fondaparinux (efficacy and safety) were most marked in patients with a GFR less than 58 mL/min per 1.73 m2; the largest differences occurred in major bleeding events. At 9 days, death, myocardial infarction, or refractory ischemia occurred in 6.7% of patients receiving fondaparinux and 7.4% of those receiving enoxaparin (hazard ratio, 0.90 [95% CI, 0.73 to 1.11]); major bleeding occurred in 2.8% and 6.4%, respectively (hazard ratio, 0.42 [CI, 0.32 to 0.56]). Statistically significant differences in major bleeding persisted at 30 and 180 days. The rates of the composite end point were lower with fondaparinux than with enoxaparin in all quartiles of GFR, but the differences were statistically significant only among patients with a GFR less than 58 mL/min per 1.73 m2.. Subgroup analyses warrant caution; the study was powered to detect noninferiority at 9 days. Fondaparinux is not approved for use in patients with ACS in the United States.. The benefits of fondaparinux over enoxaparin when administered for non-ST-segment elevation ACS are most marked among patients with renal dysfunction and are largely explained by lower rates of major bleeding with fondaparinux.

Topics: Aged; Aged, 80 and over; Angina Pectoris; Anticoagulants; Coronary Disease; Death, Sudden, Cardiac; Double-Blind Method; Enoxaparin; Female; Fondaparinux; Glomerular Filtration Rate; Hemorrhage; Humans; Kidney; Male; Middle Aged; Myocardial Infarction; Polysaccharides; Syndrome

This study reports a prospectively planned analysis of patients with acute coronary syndrome who underwent early percutaneous coronary intervention (PCI) in the OASIS-5 (Fifth Organization to Assess Strategies in Ischemic Syndromes) trial.. In the OASIS-5 trial, fondaparinux was similar to enoxaparin for short-term efficacy, but reduced major bleeding by one-half and 30-day mortality by 17%.. The OASIS-5 trial was a double-blind, randomized comparison of fondaparinux and enoxaparin in 20,078 patients with acute coronary syndrome. A total of 12,715 patients underwent heart catheterization during the initial hospitalization, and 6,238 patients underwent PCI. In the fondaparinux group, intravenous fondaparinux was given for PCI. In the enoxaparin group, no additional anticoagulant was given if PCI was <6 h from last subcutaneous dose, and additional intravenous unfractionated heparin (UFH) was given if PCI was >6 h.. Fondaparinux compared with enoxaparin reduced major bleeding by more than one-half (2.4% vs. 5.1%, hazard ratio [HR] 0.46, p < 0.00001) at day 9, with similar rates of ischemic events, resulting in superior net clinical benefit (death, myocardial infarction, stroke, major bleeding: 8.2% vs. 10.4%, HR 0.78, p = 0.004). Fondaparinux reduced major bleeding 48 h after PCI irrespective of whether PCI was performed <6 h of the last enoxaparin dose (1.6% vs. 3.8%, HR 0.42, p < 0.0001) or >6 h when UFH was given (1.3% vs. 3.4%, HR 0.39, p < 0.0001). Catheter thrombus was more common in patients receiving fondaparinux (0.9%) than enoxaparin alone (0.4%), but was largely prevented by using UFH at the time of PCI, without any increase in bleeding.. Upstream therapy with fondaparinux compared with upstream enoxaparin substantially reduces major bleeding while maintaining efficacy, resulting in superior net clinical benefit. The use of standard UFH in place of fondaparinux at the time of PCI seems to prevent angiographic complications, including catheter thrombus, without compromising the benefits of upstream fondaparinux.

Topics: Angina, Unstable; Angioplasty, Balloon, Coronary; Anticoagulants; Cohort Studies; Double-Blind Method; Enoxaparin; Female; Fondaparinux; Heparin; Humans; Male; Middle Aged; Myocardial Infarction; Polysaccharides; Syndrome; Time Factors; Treatment Outcome

In this dose-finding study, we sought to compare fondaparinux with enoxaparin in patients with acute coronary syndromes (ACS).. Fondaparinux is a synthetic pentasaccharide that selectively inhibits activated clotting factor X. It has been demonstrated as effective in preventing thromboembolic complications in orthopedic surgery.. Four doses fondaparinux (2.5, 4, 8, or 12 mg once daily) and enoxaparin (1 mg/kg twice daily) were compared, both given for three to seven days, in patients with ACS without persistent ST-segment elevation.. The rates of the combined primary end point of death, myocardial infarction, or recurrent ischemia after nine days were 27.9%, 35.9%, 34.7%, 30.3%, and 35.7% in patients allocated to fondaparinux doses of 2.5, 4, 8, and 12 mg and enoxaparin, respectively (p = NS). In the per-protocol analysis (929 patients who received adequate study drug and had adequate ST-segment monitoring), these figures were 30.0%, 43.5%, 41.0%, 34.8%, and 40.2%. Again, no dose response was observed. The lowest event rates were observed in the 2.5-mg fondaparinux group, which had significantly lower rates than the enoxaparin group as well as for 4 and 8 mg fondaparinux in the per-protocol analysis (p < 0.05). Bleeding rates were low and not different among the patient groups. No differences were observed in fondaparinux concentrations in patients with or without death, myocardial infarction, recurrent ischemia, or bleeding events.. This dose-finding study revealed no dose response for different fondaparinux doses ranging from 2.5 to 12 mg subcutaneously and suggests that the efficacy and safety of fondaparinux may be similar to that of enoxaparin. Further studies with fondaparinux in ACS might include the lowest dose (2.5 mg) investigated in this study.

Topics: Acute Disease; Adrenergic beta-Antagonists; Adult; Angioplasty, Balloon, Coronary; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Coronary Artery Bypass; Coronary Disease; Creatine Kinase; Creatine Kinase, MB Form; Dose-Response Relationship, Drug; Double-Blind Method; Electrocardiography; Enoxaparin; Female; Fibrinolytic Agents; Follow-Up Studies; Fondaparinux; Hemorrhage; Humans; Hypolipidemic Agents; Isoenzymes; Male; Middle Aged; Polysaccharides; Survival Analysis; Syndrome; Treatment Outcome; Troponin T

Topics: Aged; Arginine; Female; Fondaparinux; Heparin; Humans; Immunoenzyme Techniques; Inflammation; Pipecolic Acids; Platelet Factor 4; Polysaccharides; Sulfonamides; Syndrome; Thrombocytopenia; Treatment Outcome

Topics: Adenocarcinoma; Anticoagulants; Benzimidazoles; beta-Alanine; Dabigatran; Drug Resistance; Drug Therapy, Combination; Female; Fondaparinux; Humans; Middle Aged; Neoplasms, Unknown Primary; Polysaccharides; Syndrome; Treatment Outcome; Venous Thrombosis

Topics: Administration, Cutaneous; Angina, Unstable; Anticoagulants; Cardiac Catheterization; Comorbidity; Coronary Thrombosis; Enoxaparin; Factor X; Fondaparinux; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Polysaccharides; Syndrome; Troponin

Topics: Acute Disease; Anticoagulants; Antithrombin III; Coronary Disease; Drug Therapy, Combination; Electrocardiography; Fondaparinux; Hemorrhage; Heparin; Humans; Incidence; Myocardial Infarction; Platelet Aggregation Inhibitors; Polysaccharides; Registries; Severity of Illness Index; Syndrome; Thrombocytopenia